The Parkland-UT Southwestern PROSPR Center represents a fully coordinated, trans-disciplinary partnership of the Parkland Health System, UT Southwestern Medical Center, Simmons Cancer Center, and UT School of Public Health. Our goal is to optimize colon cancer screening through personalized regimens in our integrated safety-net clinical provider network serving a large and diverse population of under- and uninsured patients in Dallas. Three interlocking research projects will assess clinic, system, and organizational factors associated with over-, under- and guideline-based screening among this vulnerable population, and will compare benefits, harms, and costs of strategies for facilitating optimized screening regimens. Project 1 employs an in-reach strategy by implementing innovative, algorithmically driven tools in primary-care and colonoscopy clinics to collect information including patients' familial risk factors and colonoscopy findings to: identify personalized guideline-based screening regimens; characterize under- and over-screening. Project 2, a comparative effectiveness trial, compares benefits, harms and costs resulting from two system level, mailed outreach strategies for promoting effective screening: the first strategy begins with a mailed fecal immune-histochemical test kit; the second begins with a mailed invitation for colonoscopy; both include centralized processes to assure guideline-based follow up. Project 3 characterizes organizational factors at the network and clinic level that contribute to completion of screening processes and examines which organizational factors modify relationships between social disadvantage and completion of guideline-based screening processes. Parkland, the sole safety-net provider in Dallas County, is a vertically integrated delivery system that includes 11 primary care clinics caring for 32,000 adults (50-64 yrs) and has a comprehensive electronic record through which eligibility for a test, test ordering, results, referrals, and treatment are ascertainable. Through these capabilities, the Screening Process Documentation Unit will: collect accurate, clinically detailed data on all relevant processes and outcomes across the screening process, and link to the ACCR Gold-Star Texas Cancer Registry; facilitate data transfers to the national data coordinating center; and work closely with the Shared Research Resources Core to provide all data needed for Projects 1-3.